Dr. Caroline Tanner Video (Text Version)
2015 NETPR Investigator Vignette
Title: Persistent Organic Pollutants and Parkinson’s disease in Native Populations of Hawaii and Alaska
Investigator: Caroline Tanner, MD, PhD; University of California, San Francisco
I’m a clinician; I take care of patients with Parkinson’s and related disorders. And I’m interested in better treatments and understanding the causes of Parkinson’s as a way to get to better treatments. And I’m interested in the environmental exposures that people may have experienced by virtue of where they live, and how that would relate to whether or not they’re at greater risk for Parkinson’s, or whether or not—once they have Parkinson’s— they do better or worse than someone without a particular exposure.
There was an observation in Greenland that suggested that Parkinson’s was more common in the native population there. They thought this might be because of more intake of marine mammals; and marine mammals bio-concentrate persistent pollutants. We were interested in replicating this finding.
And so we did do that by identifying this population of Alaskan Natives, and finding the people with Parkinson’s, finding a similar group of people for comparison who were the same age, the same gender, and from the same area/tribal region around Alaska, and making comparisons of what they ate, what kinds of activities they did, and also habits like smoking, other dietary factors, occupation. And what we found was that Alaskan Natives who had been exposed to certain persistent organic pollutants appeared to be at greater risk of developing Parkinson’s disease—so about a two- to threefold increased risk.
But, there are other people who had high levels of these chemicals and didn’t have Parkinson’s disease. And so, we started thinking that people who have Parkinson’s may have other metabolic differences that makes them more vulnerable if they have an exposure. And so, we specifically explored a particular gene that’s called P-glycoprotein, and it codes for a transporter that’s on the cell surface that basically spits out toxicants that come into the cell, so it protects the cell.
So, we thought that people who weren’t very good at kicking out toxicant chemicals might be at greater risk if they had an exposure to [organo-] chlorine pesticides or other toxicants. And we found is that people who had a chemical exposure–and had a variant associated with a greater risk–had now, instead of twofold increased risk, four and a half-fold [to] sixfold increased risk of developing Parkinson’s. Again, a suggestion that having a genetic susceptibility and an environmental exposure in combination is what probably causes Parkinson’s in most people.
I’ve also been fortunate to be a collaborator with the Honolulu–Asia Aging Study, and they have been taking advantage of this population of men who lived in Honolulu, who were first put together to be studied for heart disease risk factors. And somewhere around 1990, they recognized that these men were now at the age at risk for neurodegenerative disorders like Parkinson’s or Alzheimer’s disease.
And some of the work that was observed there was that men who had worked in the sugar cane fields, been exposed to pesticides, worked in, you know, the pineapple fields, were at greater risk of Parkinson’s disease. So, this follows along with the whole idea about persistent organic pollutants. So, to my great pleasure, I was asked to be a consultant—went over there and helped with exams, looking for factors that increased the risk of Parkinson’s or that may lower your risk of Parkinson’s.
So, there were some really important things that came out of that study that have changed the way we think about Parkinson’s, and changed the way that we, as clinicians, practice today. One of the big ones being the recognition that men who had a reduced sense of smell were much more likely to get Parkinson’s at some point in the future than men who didn’t have that particular reduction in olfactory function. And moreover, if you looked at men who had a reduced sense of smell who didn’t get Parkinson’s during life—but you examined their brains after they’ve passed away—the changes in the brain that go along with Parkinson’s disease could be seen there, even though they hadn't yet gotten far enough to cause the symptoms of Parkinson’s.
So, that led to a very important concept that there is a prodromal period—that there’s this window of years from the time the first changes happen in the body to the time that someone manifests motor or cognitive changes of Parkinson’s—and that we, if we could tap into that window and start intervening with things that would delay or stop the development of disease, then we can prevent Parkinson’s.
So, a simple observation in a very careful prospectus study like that, has led to a totally new way of thinking about what we might be able to do at some point not too far in the future.